safety and effectiveness of a-dmdt390-bisfv(ucht1) fusion protein in subjects with mycosis fungoides

Conditions: Mycosis Fungoides

Summary: this study evaluates the effectiveness - as judged by complete response - of a single four-day treatment with the fusion protein a-dmdt390-bisfv(ucht1) compared to oral zolinza (vorinostat), in a randomized 2-arm trial after a maximum of 12 months of treatment. patient eligibility is stage ib/iib mycosis fungoides with mswat \< 50 who have never had lymphoid disease or a prior bone marrow / hsct transplant.

primary objective: this study objective is to document the incidence of complete responses compared to oral vorinostat, in a randomized 2-arm trial after a maximum of 12 months of treatment for subjects with stage ib/iib mycosis fungoides with mswat \< 50 who have never had lymphoid disease or a prior bone marrow / hsct transplant. secondary objective: to further explore the toxicity profile of a-dmdt390-bisfv(ucht1) fusion protein for subjects with mycosis fungoides who have been selected to be free from preexisting cardiac disease and never treated with campath. number of subjects: lead-in dosing: 12 / randomized: 162 patients will receive full supportive care during the course of the study. participation in the study will require iv infusions of the research agent 2 times a day for four days (protocol fda outpatient approved), as well as frequent outpatient blood draws for the first 30 days. patients with partial or complete remissions at their 1 month follow up visit will have another follow-up visit on day 60, then every three months for 1 year, followed by annual visits to assess duration of the response.

Eligibility criteria:
inclusion criteria: * subjects must have signed the current irb approved informed consent prior to registration (see informed consent). * mycosis fungoides, confirmed by biopsy or flow cytometry, without large cell transformation. * relapse or progression after 2 or more systemic therapies. note: total electron beam therapy can be counted as a systemic therapy. * disease stage as follows: * stage ib with no lymph node involvement including lymphadenopathy with mswat \<50; * stage iib with no lymph node involvement including lymphadenopathy with mswat \<50. * age 18 years. * subjects must have a performance status of \< 2 on eastern cooperative oncology group scale (see appendix a). * subjects must have normal lung function evaluated by pulse oximetry with o2 saturation values between 95-100%. * subjects must have fully recovered from toxicity of prior chemotherapy or radiation therapy. * subjects must have: * bilirubin \< 1.5 mg/dl, * transaminases \< 2.5 x uln, * albumin \> 3 gm/dl, * creatinine \< 2.0 mg/dl. * subjects who have had albumin \ 3gm dl for 14 days without an additional infusion. * subjects must have a normal echocardiogram (ef \> 50% normal) without any evidence of cardiac chamber hypertrophy, dilatation or hypokinesis. * females and males must be willing to use an approved form of birth control while on this study and for 2 weeks after completion. * subjects must have a pretreatment anti-dt titer of 20 μg/ml or less. subjects with titers between 21 and 35 μg/ml will have an additional anti-dt neutralization test using subject's serum and a-dmdt390-bisfv(ucht1). if neutralization is not found these titers will be considered acceptable. exclusion criteria: * failure to meet any of the criteria. * inability to give informed consent because of psychiatric problems, or complicated medical problems. * allergic to diphtheria toxin a component of the study drug a-dmdt390-bisfv(ucht1). * serious concurrent medical problems, uncontrolled infections, or disseminated intravascular coagulopathy (dic), hepatic cirrhosis, or chronic kidney disease. * cns leukemia. * preexisting cardiovascular disease. the only exception being well controlled essential hypertension with a sitting blood pressure (b.p.) of \ 8 months ago. subjects receiving a beta-blocker for hypertension should be converted to another antihypertensive drug class 2-3 weeks before receiving the study drug to prevent a drug-drug interaction reactive tachycardia. angiotensin inhibitors, angiotensin receptor blockers and calcium channel blockers are all acceptable. a past history of any of the following conditions is considered as exclusions to study participation: * congestive heart failure, * atrial fibrillation, * pulmonary hypertension, * anticoagulant drug therapy, * thromboembolic events, * cardiomyopathy or a myocardial infarction within the past 8 months. the pi and the clinical coordinator will be asked to verify that their referred subjects do not have these exclusionary histories listed in 3.2 and a copy of this verification must be sent to the sponsor before the sponsor will approve of enrollment. referring physicians will not need to sign. * pregnant or nursing women will be excluded from study. * history of cirrhosis of the liver based on the child-pugh score of class b or c are not eligible to participate. * prior treatment with alemtuzumab (campath) or similar agents or procedures that depress blood t cell counts to below 50% of the lower limit of normal. * prior history of bone marrow transplant or hsct is an exclusion. * prior treatment with vorinostat (prior treatment with vorinostat for lead-in dosing arm is acceptable).

Keywords: mf ctcl cutaneous t cell lymphoma